Pediatric renal tumors account for about six percent of all childhood cancers in the United States. (1) The survival rate of pediatric patients with kidney tumors varies according to the respective pathology. Wilms' tumor has a good prognosis, with about an 80% cure rate; Clear Cell Sarcoma (CCS) of the kidney has a fair prognosis with about a 60% cure rate; whereas Rhabdoid tumors (RTK) of the kidney has a poor prognosis, with a cure rate of only about 10%. Despite this association, it is not uncommon to find that the behavior of a specific tumor is disparate with its pathologic diagnosis. Unfortunately, there are no recognized biologic markers (except for clinical stage and tumor type) for predicting prognosis or for guiding treatment, follow-up and counseling of pediatric patients with renal tumors.
Apoptosis, or programmed cell death, is the process by which activated cells undergo a suicide program that results in individual cell death. (2) It is a highly orchestrated process where cells die in a regulated fashion. Aberration in the process of apoptosis may contribute to the pathogenesis of certain tumors. (3) It has been shown that pro-apoptotic receptors were expressed at greater levels in Wilms' tumors of good prognosis, compared to CCS or RTK. (4) Surprisingly, no association was found with anti-apoptotic factors like Bcl-2 or Bcl-XL and prognosis.
An excess of apoptosis inhibitors could protect dividing cells from dying, and thus contribute to tumorigenicity. A related family of Inhibitors of Apoptosis proteins (IAP) has been described in many species and these proteins block apoptosis by direct inhibition of downstream effector caspases in the pathway of cell death. (5,6) A novel member of the IAP gene family designated Survivin was recently described and shown to be associated with tumors of poor prognosis. (7-10) Survivin is selectively expressed in tissues during development but not in terminally differentiated mature tissue and is also expressed in several pediatric renal tumors tested. (11) Survivin appears to block default induction of apoptosis during mitosis, and when over expressed in cancer cells, Survivin may permit aberrant proliferation through mitosis.
Currently, for many types of tumors there are no available markers specific for the tumor type. Thus, for these tumor types, treatment cannot be specifically guided nor can prognosis be predicted. Therefore, there is an ongoing need for methods and kits to predict recurrent tumor growth, in particular solid tumors and hematologic cancers. Such an indicator would be helpful not only for guiding the patient as to outcome, but also for selecting treatment groups as well as follow-up during treatment of disease.